{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Shi R"],"funding":["Male Contraceptive Initiative","YourChoice Therapeutics","National Institute of Child Health and Human Development"],"pagination":["1568-1605"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12833862"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["69(2)"],"pubmed_abstract":["The retinoic acid receptor alpha (RARα) has emerged as a compelling genetically and pharmacologically validated target for nonhormonal male contraception due to its essential role in spermatogenesis. In the present study, a search for specific inhibitors of RARα utilized systematic linker bioisosterism, hydrophobic core modification, and iterative structure-activity relationship refinement, identified <b>the</b> acid <b>9</b>, a pyrrole-linked analog that potently inhibits RARα (IC<sub>50</sub> = 1.2 nM) with >300-fold selectivity over RARβ and RARγ. Sprague-Dawley rat studies with the sodium salt of <b>9</b>, <b>YCT-529</b>, showed good oral bioavailability and dose-proportional pharmacokinetics without drug accumulation after 28 days of dosing. Once-daily oral administration (0.75 mg/kg "],"journal":["Journal of medicinal chemistry"],"pubmed_title":["From Discovery to Clinical Trial: YCT-529, an Oral NonHormonal Male Contraceptive Targeting the Retinoic Acid Receptor Alpha."],"pmcid":["PMC12833862"],"funding_grant_id":["5P50HD093540","HHSN275201300017C"],"pubmed_authors":["Al Noman MA","Shi R","Hawkinson JE","Chung SSW","Bakshi A","Mannowetz N","Georg GI","Wong HL","Haque E","Maitra S","Cheryala N","Wolgemuth DJ","Naqvi T"],"additional_accession":[]},"is_claimable":false,"name":"From Discovery to Clinical Trial: YCT-529, an Oral NonHormonal Male Contraceptive Targeting the Retinoic Acid Receptor Alpha.","description":"The retinoic acid receptor alpha (RARα) has emerged as a compelling genetically and pharmacologically validated target for nonhormonal male contraception due to its essential role in spermatogenesis. In the present study, a search for specific inhibitors of RARα utilized systematic linker bioisosterism, hydrophobic core modification, and iterative structure-activity relationship refinement, identified <b>the</b> acid <b>9</b>, a pyrrole-linked analog that potently inhibits RARα (IC<sub>50</sub> = 1.2 nM) with >300-fold selectivity over RARβ and RARγ. Sprague-Dawley rat studies with the sodium salt of <b>9</b>, <b>YCT-529</b>, showed good oral bioavailability and dose-proportional pharmacokinetics without drug accumulation after 28 days of dosing. Once-daily oral administration (0.75 mg/kg ","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-06-09T07:21:00.425Z","creation":"2026-06-09T03:12:00.416Z"},"accession":"S-EPMC12833862","cross_references":{"pubmed":["41524264"],"doi":["10.1021/acs.jmedchem.5c03051"]}}